Research Blog

LDH: How Low Can You Go?

Lactate dehydrogenase (LDH) is an important enzyme in energy production. Various forms of LDH are found in almost every cell in the body, with the highest amounts found in muscle, heart, lungs, liver, kidney, and blood cells. LDH helps produce ATP under anaerobic conditions, i.e., when oxygen is in short supply. LDH can help provide fuel during hypoglycemia so insufficient LDH may contribute to persistent hypoglycemia.

Low levels of LDH in the blood are uncommon though lower levels may be seen with excess ascorbic acid intake (Farhana 2023) or pesticide exposure, especially in the absence of adequate personal protective gear (Hernández 2006).

While lower LDH is uncommon and usually not considered harmful, lactate dehydrogenase-A deficiency, also known as glycogen storage disease XI, can be harmful. This rare genetic disorder is associated with (NIH):

Fatigue
Muscle pain
Cramping during exercise (exercise intolerance)
Muscle breakdown
Red/brown urine due to myoglobin breakdown
Kidney damage
Skin rashes

Source: Forkasiewicz, Agata et al. “The usefulness of lactate dehydrogenase measurements in current oncological practice.” Cellular & molecular biology letters vol. 25 35. 9 Jun. 2020, doi:10.1186/s11658-020-00228-7 This article is licensed under a Creative Commons Attribution 4.0 International License

On the other hand, elevated LDH may be associated with muscle or tissue injury, trauma, liver disease, kidney disease, pancreatitis, cancer, anemia, heart attack, and infectious disease. Levels may be falsely elevated by medications, including anesthetics, aspirin, alcohol, narcotics, and procainamide (Farhana 2023).

Severe inflammation, tissue necrosis, and uncontrolled hyperglycemia may also be associated with elevated LDH (Hsieh 2022).

Measuring the various isoenzyme forms of LDH can help identify the tissue that it is associated with (Farhana 2023).

LDH increase can serve as a prognostic marker of cancer progression for different types of cancer. LDH also serves as one of the important diagnostic markers of cutaneous lymphoma. The concentration of LDH-5 is demonstrated as a predictor of radiotherapy and chemotherapy response in cancer patients. LDH is useful in evaluating metastatic cancer patients. Contrarily, LDH-5 serves as a marker for radio-sensitization.
The enzymes can function to monitor progressive conditions such as muscular dystrophy or HIV infection.
In sports medicine, LDH potentially indicates muscle response to training, with an increase in skeletal and cardiac muscles after 3-5 hours of training.
If LDH-1 is found to be greater than LDH-2, it indicates myocardial infarction, with a ‘flipped’ ratio of LDH-1/LDH-2 greater than 1. The increase in LDH persists for approximately ten days. It increases at 12 hours and peaks at 24-48 hours. A very high level thus indicates acute myocardial infarction.
Greater than a 50 times increase in LDH-1 and LDH-2 indicates megaloblastic anemia.
Increased LDH-5 in serum is a marker for muscular dystrophy.
A ten times increase in serum LDH indicates toxic hepatitis with jaundice.
An increase in LDH-3 is associated with the massive destruction of platelets as in pulmonary embolism.
LDH is used to assess the nature, or pathological accumulation of pleural, peritoneal, or pericardial fluids. Serum LDH, compared to serous fluid LDH, helps in distinguishing exudate from transudate effusions.
In patients with non-seminomatous testicular cancer LDH is used as a staging (S classification) marker.

References

Farhana, A., & Lappin, S. L. (2023). Biochemistry, Lactate Dehydrogenase. In StatPearls. StatPearls Publishing.

Hernández, Antonio F et al. “Influence of exposure to pesticides on serum components and enzyme activities of cytotoxicity among intensive agriculture farmers.” Environmental research vol. 102,1 (2006): 70-6. doi:10.1016/j.envres.2006.03.00

Hsieh, Yu-Shan et al. “Is the level of serum lactate dehydrogenase a potential biomarker for glucose monitoring with type 2 diabetes mellitus?.” Frontiers in endocrinology vol. 13 1099805. 15 Dec. 2022, doi:10.3389/fendo.2022.1099805

NIH. Lactate Dehydrogenase Deficiency. https://medlineplus.gov/download/genetics/condition/lactate-dehydrogenase-deficiency.pdf